tetano
Editor, Senior Moderator
Front Immunol
. 2024 Jun 18:15:1379570.
doi: 10.3389/fimmu.2024.1379570. eCollection 2024. Extracellular matrix remodelling pathway in peripheral blood mononuclear cells from severe COVID-19 patients: an explorative study
Sarah Louise Murphy[SUP] 1 2 [/SUP], Nora Reka Balzer[SUP] 3 4 5 [/SUP], Trine Ranheim[SUP] 1 [/SUP], Ellen Lund Sagen[SUP] 1 2 [/SUP], Camilla Huse[SUP] 1 2 6 [/SUP], Vigdis Bjerkeli[SUP] 1 2 [/SUP], Annika E Michelsen[SUP] 1 2 [/SUP], Ane-Kristine Finbråten[SUP] 7 [/SUP], Lars Heggelund[SUP] 8 9 [/SUP], Anne Ma Dyrhol-Riise[SUP] 2 10 [/SUP], Anders Tveita[SUP] 11 12 [/SUP], Aleksander Rygh Holten[SUP] 2 13 [/SUP], Marius Trøseid[SUP] 1 2 14 [/SUP], Thor Ueland[SUP] 1 2 15 [/SUP], Thomas Ulas[SUP] 3 4 5 [/SUP], Pål Aukrust[SUP] 1 2 14 [/SUP], Andreas Barratt-Due[SUP] 12 16 [/SUP], Bente Halvorsen[SUP] 1 2 6 [/SUP], Tuva Børresdatter Dahl[SUP] 1 [/SUP]
Affiliations
There is a reciprocal relationship between extracellular matrix (ECM) remodelling and inflammation that could be operating in the progression of severe COVID-19. To explore the immune-driven ECM remodelling in COVID-19, we in this explorative study analysed these interactions in hospitalised COVID-19 patients. RNA sequencing and flow analysis were performed on peripheral blood mononuclear cells. Inflammatory mediators in plasma were measured by ELISA and MSD, and clinical information from hospitalised COVID-19 patients (N=15) at admission was included in the analysis. Further, we reanalysed two publicly available datasets: (1) lung tissue RNA-sequencing dataset (N=5) and (2) proteomics dataset from PBCM. ECM remodelling pathways were enriched in PBMC from COVID-19 patients compared to healthy controls. Patients treated at the intensive care unit (ICU) expressed distinct ECM remodelling gene profiles compared to patients in the hospital ward. Several markers were strongly correlated to immune cell subsets, and the dysregulation in the ICU patients was positively associated with plasma levels of inflammatory cytokines and negatively associated with B-cell activating factors. Finally, our analysis of publicly accessible datasets revealed (i) an augmented ECM remodelling signature in inflamed lung tissue compared to non-inflamed tissue and (ii) proteomics analysis of PBMC from severe COVID-19 patients demonstrated an up-regulation in an ECM remodelling pathway. Our results may suggest the presence of an interaction between ECM remodelling, inflammation, and immune cells, potentially initiating or perpetuating pulmonary pathology in severe COVID-19.
Keywords: COVID-19; SARS-CoV-2; extracellular matrix; immune response; lung pathology.
. 2024 Jun 18:15:1379570.
doi: 10.3389/fimmu.2024.1379570. eCollection 2024. Extracellular matrix remodelling pathway in peripheral blood mononuclear cells from severe COVID-19 patients: an explorative study
Sarah Louise Murphy[SUP] 1 2 [/SUP], Nora Reka Balzer[SUP] 3 4 5 [/SUP], Trine Ranheim[SUP] 1 [/SUP], Ellen Lund Sagen[SUP] 1 2 [/SUP], Camilla Huse[SUP] 1 2 6 [/SUP], Vigdis Bjerkeli[SUP] 1 2 [/SUP], Annika E Michelsen[SUP] 1 2 [/SUP], Ane-Kristine Finbråten[SUP] 7 [/SUP], Lars Heggelund[SUP] 8 9 [/SUP], Anne Ma Dyrhol-Riise[SUP] 2 10 [/SUP], Anders Tveita[SUP] 11 12 [/SUP], Aleksander Rygh Holten[SUP] 2 13 [/SUP], Marius Trøseid[SUP] 1 2 14 [/SUP], Thor Ueland[SUP] 1 2 15 [/SUP], Thomas Ulas[SUP] 3 4 5 [/SUP], Pål Aukrust[SUP] 1 2 14 [/SUP], Andreas Barratt-Due[SUP] 12 16 [/SUP], Bente Halvorsen[SUP] 1 2 6 [/SUP], Tuva Børresdatter Dahl[SUP] 1 [/SUP]
Affiliations
- PMID: 38957465
- PMCID: PMC11217192
- DOI: 10.3389/fimmu.2024.1379570
There is a reciprocal relationship between extracellular matrix (ECM) remodelling and inflammation that could be operating in the progression of severe COVID-19. To explore the immune-driven ECM remodelling in COVID-19, we in this explorative study analysed these interactions in hospitalised COVID-19 patients. RNA sequencing and flow analysis were performed on peripheral blood mononuclear cells. Inflammatory mediators in plasma were measured by ELISA and MSD, and clinical information from hospitalised COVID-19 patients (N=15) at admission was included in the analysis. Further, we reanalysed two publicly available datasets: (1) lung tissue RNA-sequencing dataset (N=5) and (2) proteomics dataset from PBCM. ECM remodelling pathways were enriched in PBMC from COVID-19 patients compared to healthy controls. Patients treated at the intensive care unit (ICU) expressed distinct ECM remodelling gene profiles compared to patients in the hospital ward. Several markers were strongly correlated to immune cell subsets, and the dysregulation in the ICU patients was positively associated with plasma levels of inflammatory cytokines and negatively associated with B-cell activating factors. Finally, our analysis of publicly accessible datasets revealed (i) an augmented ECM remodelling signature in inflamed lung tissue compared to non-inflamed tissue and (ii) proteomics analysis of PBMC from severe COVID-19 patients demonstrated an up-regulation in an ECM remodelling pathway. Our results may suggest the presence of an interaction between ECM remodelling, inflammation, and immune cells, potentially initiating or perpetuating pulmonary pathology in severe COVID-19.
Keywords: COVID-19; SARS-CoV-2; extracellular matrix; immune response; lung pathology.